What is a memory and how is it recorded and stored at the molecular level? New photo-imaging technology is beginning to give researchers some answers. Read more...

In response to stimuli, neural networks fire flurried electrical responses
that leave neurological traces like crumb trails. These can be eliminated or
strengthened for long-term recall. But understanding how this happens is
daunting due to the complexity of the connections and sheer number of
neurons in the cortex.

Now, writing in the journal Proceedings of the National Academy of Sciences,
researchers describe a new method combining 3D imaging with computational
methods to simultaneously track how thousands of neurons respond to external
stimuli in the cortex of mice, long-term.

“There are a lot of activities going on in the cortex and it’s really hard to
piece out which neurons are responsible for long-term memory,” said the
study’s corresponding author, JiSong Guan, Principle Investigator at the
Center for Life Sciences at Tsinghua University in China. “For the first
time, we’ve directly shown how context environments can specifically
activate a very small portion of neurons, and this can be reactivated during
recall of memory.”

The team first began by familiarizing mice with three distinct
environment-specific trials over a two-month period. To track the neurons
activated in cortical circuits during each behavioral trial, they
fluorescently tagged early growth response protein (EGR1), which is normally
expressed during high-frequency neuronal stimulation and long-term learning
processes.

Then the researchers used two-photon imaging technology to visualize neuronal
activity in 3D slices of the brain and using a newly developed automatic
recognition algorithm, quantitated and reconstructed the activity of
thousands of individual neurons in each mouse over time.

The team ultimately found task-specific neuronal activation in cortical layer
II, but was surprised to see later activation in multiple cortical regions.

“We were originally expecting some specific region of the cortex to have a
strong response to a typical memory because some areas are more important
than others,” explained Guan. “But we found that context memories show
specific storage in almost each individual cortical area as a sparse
response, so that was kind of surprising to us.”

According to Guan, this technology may be used in studies of autism or
schizophrenia to observe how neural network responses change in mouse models
with physiological disease. For now, the group plans investigate how
cortical layer II forms the memory traces.

“We want to better understand how those neural circuits gather together to
form a specific response in a very complicated environment,” said Guan. “How
those memories change their location and gradually build the remote memory
in the cortex is still an important question to ask.”